Synthesis of Medium‐ and Large‐Ring Compounds Initiated by Photochemical Decarboxylation of ω‐Phthalimidoalkanoates

Abstract

The synthesis of a variety of hydroxylactams from w-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1,5-dione 7) to 26 (cyclodipeptide 26e). Ground-state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radials (Scheme 4). Spacer groups investigated were alkyl chains (C3-Cll: 5c-h, lla, 12), ether (16, 18), ester (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intravs. intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cJ products 11 and 12) in contrast to comparable singlet reactions. Except for the lactones 22, all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b), probably the consequence of a strong intramolecular H-bond (Scheme 10).

Microphotochemistry: 4,4'-Dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides

“…Alternatively, back electron transfer (BET) and protonation generates the simple decarboxylation products 2 and 5 . Path A thus mirrors the mechanism proposed for acetone sensitization [43]. In contrast to carboxylates (for MeCO 2 − calc.…”

Synthesis of Cyclic Peptides by Photochemical Decarboxylation of N‐Phthaloyl Peptides in Aqueous Solution

“…In a first series of photochemically active dipeptides, we prepared compounds 3a ± f (N(Pht)Gly-AA 2 ) with increasing chain length of the second amino acid (AA 2 ) component. The diglycine and the glycyl-b-alanine substrates 3a,b (not shown) have already been described as photochemically active but only gave decomposition and simple decarboxylation products [2]. From the elongated starting materials 3c ± 3f, however, we obtained the lactams 4c ± 4f in medium yields through photolysis in H 2 O in the presence of small amounts of acetone and 0.5 equiv.…”

“…± In the last years, we have elaborated the synthetic applicability of the intramolecular photoinduced decarboxylation of electronically excited phthalimides, originally described in 1991 [1]. In a first attempt to evaluate the scope and limitation of this reaction with respect to the dimension of a flexible hydrocarbon chain linking the electron acceptor with the electron donor (phthalimide and carboxylate, respectively), we discovered that macrocyclic amines can be prepared in high yields even without the use of dilution conditions (Scheme 1) [2]. The intermolecular version of this reaction was subsequently discovered and proceeds with high efficiency and flexibility when potassium alkylcarboxylates are used as the electron-donor components and N-alkylated phthalimides as the acceptors [3].…”

“…The e-aminocaproic acid derived substrate C, upon PET, gives the corresponding cyclization product H in high yields (Scheme 4) [1] [2]. Due to the conformationally flexible hydrocarbon chain, both the remote and proximate states Ia,b can be involved in the excitation and electron transfer steps.…”

Formation of Six‐Membered (and Larger) Rings

“…Acetone (which also acts as photosensitizer) containing a small amount of water is the solvent of choice, whereas potassium carbonate is the ideal base to enhance cyclization versus simple decarboxylation and ring opening of the phthalimide [4].…”